Trafficking mechanisms of P-type ATPase copper transporters

• Type of Material: Article
• Authors: Cortnie Hartwig, Emory University; Stephanie Zlatic, Emory University; Melissa Wallin, Augusta University; Alysia Vrailas-Mortimer, Illinois State University; Christoph J. Fahrni, Georgia Institute of Technology; Victor Faundez, Emory University
• Language: English
• Date: 2019-08-01
• Publisher: Current Biology Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ceb.2019.02.009
• Title of Journal or Parent Work: Current Opinion in Cell Biology
• Volume: 59
• Start Page: 24
• End Page: 33
• Grant/Funding Information: This work was supported by a grant from the National Institutes of Health R01AG060285 to VF R15AR070505 to AVM, and R01GM67169 to CJF.; CH is supported by the FIRST postdoctoral fellowship NIH 5K12GM000680.
• Keywords: Life Sciences & Biomedicine; Menkes disease; Wash complex; Science & Technology; Cytochrome-C-oxidase; Kinky-hair disease; Parkinsons disease (PD); Dependent trafficking; Cell Biology; Mitochondrial metallochaperone SC01; Spinal muscular atrophy; Functional analysis; Regulated trafficking
• Research Categories: Engineering, Biomedical; Chemistry, Biochemistry; Biology, Cell

Abstract

Copper is an essential micronutrient required for oxygen-dependent enzymes, yet excess of the metal is a toxicant. The tug-of-war between these copper activities is balanced by chaperones and membrane transporters, which control copper distribution and availability. The P-type ATPase transporters, ATP7A and ATP7B, regulate cytoplasmic copper by pumping copper out of cells or into the endomembrane system. Mutations in ATP7A and ATP7B cause diseases that share neuropsychiatric phenotypes, which are similar to phenotypes observed in mutations affecting cytoplasmic trafficking complexes required for ATP7A/B dynamics. Here, we discuss evidence indicating that phenotypes associated to genetic defects in trafficking complexes, such as retromer and the adaptor complex AP-1, result in part from copper dyshomeostasis due to mislocalized ATP7A and ATP7B.